Abstract
Our studies of the brain microvascular system have focused on some aspects not commonly
studied by other research groups because we use some techniques not often used by
others. Our observations tend to add new details to the pathological picture rather
than contradict the mainstream findings. We use large, thick celloidin sections which
provide a three dimensional view of vascular networks, and alkaline phosphatase (AP)
staining which allows one to differentiate between afferent and efferent vessels.
We found millions of lipid microemboli in the brains of patients after cardiac surgery,
and concluded that they caused vascular dementia in many patients. We previously proposed
an animal model of vascular dementia using brain irradiation, which induces capillary
loss. Lipid emboli might also be used to create an animal model of vascular dementia.
The deep white matter is vulnerable to chronic hypoperfusion because the blood vessels
supplying this region arise from the border-zone and have the longest course of all
vessels penetrating the cerebrum. In cases with leukoaraiosis (LA), we found periventricular
venous collagenosis (PVC), resulting in stenosis. Thirteen of 20 subjects older than
60 years had PVC, and 10 of 13 subjects with severe PVC had LA. Vascular stenosis
might induce chronic ischemia and/or edema in the deep white matter, leading to LA.
We suggest three mechanisms for a possible genetic predisposition to PVC: i) a predisposition
to excessive venous collagenosis; ii) an indirect effect that causes chronic periventricular
ischemia with a reactive over-production of collagen; and iii) mechanical damage to
small vessels due to increased pulsatile motion. We found tortuous arterioles supplying
the deep white matter beginning at about age 50. We also found a trend toward an increase
in tortuosity in LA. If tortuosity is a factor in LA, it is probably significant in
only a subset of cases. String vessels, remnants of capillaries, occur commonly in
the brain, and are increased in ischemia, AD, and irradiation. Capillary injury or
shutdown of blood flow can lead to capillary loss and string vessel formation. We
found string vessels in brains from preterm babies to the very old. They seem to disappear
after some months or years. We found an early loss of capillaries in LA, followed
in a few years by the disappearance of string vessels. LA lesions do not progress
to cortical cavitating lesions. Our findings raise three questions. 1. Why is the
capillary loss arrested before infarction? 2. Why is there a floor below which the
vascular density will not fall? 3. Why does the process which initiates string vessels
shut down? We explain the vascular changes in LA as follows. LA induces apoptosis
with loss of oligodendrocytes. Capillaries and neuropil are lost. Increased oxygen
extraction from the blood in the deep white matter in LA implies that there are too
many cells for the remaining capillaries. Thus, the capillaries appear to die first.
But why do they stop dying? Perhaps a minimum number of capillaries are needed to
transport the arterial blood to the venous system. Once the capillaries stop dying,
no more string vessels are formed, and the string vessels gradually disappear.
Keywords
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Published online: March 06, 2009
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© 2009 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
